Sasse, the president of Midland University and former assistant secretary of the Department of Health and Human Services, is battling for the conservative mantle in the race to replace retiring Sen. Mike Johanns (R-Neb.).

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The race has split national conservative groups. Sasse has the backing of Rep. Paul Ryan (R-Wis.), the Club for Growth and the Senate Conservatives Fund, while his opponent, former Nebraska Treasurer Shane Osborne (R), is backed by FreedomWorks.

"Ben Sasse has been called ObamaCare's Nebraska nemesis," the ad's narrator says as the National Review cover story is displayed.

"I'm one of the few it seems who read and studied ObamaCare's 2,300 pages. It's worse than you think," he says in the ad. "We have to choose the strongest, most conservative Nebraska voice to send to Washington."

Sasse's campaign manager says there is a "significant buy" behind the ad and it is being aired statewide.